Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution

Abstract Introduction Although rhinitis is among the most common diseases worldwide, rhinitis prevalence in the general adult population is unclear and definitions differ widely. Objective To summarize the literature on rhinitis prevalence in the general adult population and to assess: (1) the prevalence according to different rhinitis definitions overall and in different regions of the world, and (2) the evolution of rhinitis prevalence over time. Methods We conducted an extensive literature review of publications including rhinitis prevalence using Pubmed and Scopus databases up to October 2020. We classified the definitions into three categories: unspecified rhinitis, allergic rhinitis (AR), and nonallergic rhinitis (NAR). Results Among 5878 articles screened, 184 articles were included, presenting 156 different definitions of rhinitis. Rhinitis prevalence ranged from 1% to 63%. The overall median prevalences of unspecified rhinitis, AR and NAR were 29.4%, 18.1% and 12.0%, and they varied according to the geographical location. Rhinitis prevalence tended to increase over time. Conclusions This review highlights the great heterogeneity of the definitions. The majority of studies had focused on AR, while only a few epidemiological data exist on NAR. We found geographical variability in rhinitis prevalence. Most of studies reported an increase of rhinitis prevalence over the last decades.

on NAR. We found geographical variability in rhinitis prevalence. Most of studies reported an increase of rhinitis prevalence over the last decades.

S C H L Ü S S E L W Ö R T E R
Allergische Rhinitis, Epidemiologie, Nicht-allergische Rhinitis, Prevalenz, Rhinitis

P A L A B R A S C L A V E
rinitis alérgica, epidemiología, rinitis no alérgica, prevalencia, rinitis

| INTRODUCTION
Rhinitis is among the most common chronic diseases in the world. 1 Rhinitis is a generic term describing nasal symptoms resulting from inflammation and/or dysfunction of the nasal mucosa. 2 In this study, we will not consider acute infectious rhinitis that is often due to common cold or flu. The two other main phenotypes of rhinitis are allergic rhinitis (AR) and nonallergic rhinitis (NAR): AR refers to nasal symptoms that are triggered by Immunoglobulin E (IgE)-mediated response to exposure to allergens, while NAR refers to a heterogeneous group of nasal symptoms without allergic sensitization. 3 Several definitions of rhinitis have been used in epidemiological studies, some of them defining rhinitis as a unified entity, while others define AR and NAR separately. To date, literature reviews on rhinitis prevalence have focused solely on AR. [4][5][6][7] To our knowledge, the last extensive review of the literature on the prevalence of AR worldwide was conducted by the AR and its Impact on Asthma (ARIA) in 2008, and at that time the identified studies were mainly conducted in Europe or in the United States. 4 In 2012, a literature review was conducted on the prevalence of AR outside North America and Europe 5 and two recent literature reviews reported prevalence of AR only in China. 6,7 Therefore, there is no recent literature review on rhinitis prevalence worldwide.
Regarding the worldwide prevalence of rhinitis among children, the International Study of Asthma and Allergies in Childhood (ISAAC), which is considered as the landmark study in this field, reported in 2004 a prevalence of self-reported current nasal symptoms of 31.7% (ranging from 11.9% to 80.6%) based on data from 97 countries. 8 Among adult populations, the largest international multicenter study is the European Community Respiratory Heath Survey (ECRHS), and it estimated a median prevalence of self-reported nasal allergies of 20.9% (ranging from 9.5% to 40.9%) in 1995. 9 That study did not estimate the overall prevalence of rhinitis nor that of NAR, and even though it included altogether 20 countries, they were mainly from the same geographical area, that is from the Western Europe. It is commonly proposed in the literature that rhinitis prevalence has increased in recent decades, 4 but there is no literature review on this topic.
In summary, many different definitions of rhinitis have been applied, and the majority of the studies have focused on AR, with only a few studies focusing on NAR. Moreover, the estimates of rhinitis prevalence in adults in different parts of the world are still poorly known.
The objective of the present study was to conduct an extensive literature review on rhinitis prevalence in general adult population around the world. This review describes rhinitis prevalence according to different definitions and worldwide. It also aims to describe the temporal evolution of rhinitis prevalence.

| METHODS
The present literature review on rhinitis prevalence was performed according to the four-phase flow diagram presented in the PRISMA statement as follows: identification, screening, defining eligibility, and inclusion ( Figure 1).

| Information sources, search strategy, selection process and eligibility criteria
The literature search used the computerized bibliographic databases PubMed and Scopus and included all the existing literature up to October 13, 2020. We searched for the terms "rhinitis" or "hay fever" combined with "epidemio*" or "preval*" in the title or abstract. The only limitation we applied was that the studies had to be written in English, French, or Spanish language. Additional records from the references of the literature reviews and of the eligible publications identified in the search were included. The articles were first screened based on their title and abstract, and then articles of interest were read entirely to assess their eligibility.
Articles were selected according to the following criteria: the articles were required to (1) be an original epidemiological study, (2) include prevalence data on rhinitis, AR and/or NAR, (3) be based on a general adult population or a population including all ages. As this study focuses on rhinitis prevalence in general population, we excluded studies focusing only on specific subpopulations such as children, students, farmers, exclusively in men, or women. We also excluded studies that were conducted in specific health centers or allergy clinics and studies that did not contain any information on the definition of rhinitis, or that did not provide any calculable rhinitis prevalence in the general population.

| Data items
The following data were collected: (1) the year of publication, (2) the country where the study was conducted, (3) the period during which the study was conducted, (4) the size and age range of the studied population, (5) the study design, including cross-sectional and/or longitudinal, (6) the method applied to assess the prevalence, including interview or self-report, and (7) the definition applied for rhinitis.
When not directly reported in the article, the prevalence was calculated based on the available data, applying the following formula: the number of participants with rhinitis divided by the total number of participants. We reported the prevalence in adults only if available, otherwise we reported the prevalence of the population including adults and children.

| Classification of the data
We have categorized the different definitions of rhinitis into three categories as follows: "unspecified rhinitis" refers to a definition of rhinitis that did not specify whether it was allergic or nonallergic; AR refers to a definition that included the term "AR" and/or "hay fever"  and/or assessment of allergic sensitization by skin tests and/or serum specific IgE; NAR refers to a definition that excluded AR and/or referred to triggers known to induce NAR, such as cold and dry air, temperature change, airborne chemical irritants, spicy food, alcoholic beverages, exercise, use of tobacco, anti-inflammatory drugs, stress, and/or printer ink. In addition, we have further subcategorized unspecified rhinitis, AR and NAR according to the method on which the definition was based: "symptoms-based definition" which refers to a definition that is based on a question asking from the participant himself/herself about the presence of rhinitis or nasal symptoms; while "doctor diagnosis-based definition" of rhinitis was based on asking a question referring to a previous self-reported medical diagnosis of rhinitis or on a diagnosis made by a physician for the study.

| Statistical methods
Mean prevalences were calculated for the unspecified rhinitis, AR, and NAR applying Microsoft Excel®. For each definition, we calculated the crude mean, median and confidence intervals based on binomial distribution with R 4.3. To compare rhinitis prevalence according to different regions of the world, prevalences were first grouped by country and then the countries were stratified by continent.
To study the evolution of rhinitis prevalence over time, we selected studies that had repeated measures of the prevalence using the same definition and comparable populations over time.
As a complementary analysis, we calculated the rhinitis prevalences based solely on the ISAAC and ECRHS questions that are from the two largest international studies on rhinitis and that were used in several studies included in the present literature review.
We also conducted sensitivity analyses with more restrictive definitions and populations to obtain less biased prevalences of unspecified rhinitis, AR and NAR in the general adult populations. We conducted sensitivity analyses based on the following two criteria: (1) To include only more "reliable" definitions of rhinitis, we excluded those studies in which the definition was/had been based on: (a) questions that did not exclude explicitly common cold or flu; (b) questions that included other allergic diseases in the same item, such as conjunctivitis or eczema; (c) questions that were limited to the time of the survey; (d) questions that did not specify when rhinitis was or had been present, and (e) questions that focused solely on specific sub-phenotypes of rhinitis such as rhinoconjunctivitis, seasonal AR, or peri-annual rhinitis.
(2) To have a more homogeneous adult population, we excluded studies that reported prevalences based on populations: (a) that combined adults and children (i.e., under the age of 16 years), and (b) that included the elderly only (i.e., above the age of 60 years).

| RESULTS
After excluding duplicates, a total of 5878 records were identified.
Altogether 184 articles were included in the present review ( Figure 1, Appendix 1 in Supporting Information S1) with 426 reported prevalences of unspecified rhinitis, AR or NAR.

| Evolution in the rhinitis prevalence over time
The evolution over time of rhinitis prevalence within the same population or similar populations and applying the same definition in the same geographical region are presented in Figure 3. Table S3 in   Supporting Information S3 provides details of the prevalences by country.
In the America, in Brazil a 10% decrease in the rhinitis prevalence was reported between 2011 and 2018. 22 In the United States, the National Health and Nutrition Examination Survey (NHANES) reported that episodes of hay fever in the past 12 months increased from 11.8% to 13.6% between 2007 and 2012. In the National Health Interview Survey (NHIS), the prevalence of AR decreased from 9.3% in 1997 to 7.3% in 2018.

In Asia, the Korean National Health and Nutrition Examination
Survey reported that the prevalence of AR increased between 1998 and 2017 from 1.0% to 17.1%. 23,24 In Europe, studies from Denmark, 25,26 Finland, 27,28 France, 29,30 Germany, 31 Italy, 32 Russia, 27 Scotland, 33   We conducted an extensive literature search using the most commonly used keywords for rhinitis and AR, namely "rhinitis" and "hay fever". In an additional search, we also considered to use keywords "nose symptoms" or "nasal symptoms" as synonyms for rhinitis, but the results of these searches only provided additional articles that referred to differential diagnoses of rhinitis, such as COVID-19 or nasal polyps. Therefore, these terms were not included in the main search. As we have limited this review to articles published in English, French and Spanish, it is possible that we may have omitted some prevalence data from articles published in other languages.
We found a total of 156 rhinitis definitions in the present literature review, so we decided to classify them into three distinct categories: unspecified rhinitis, AR and NAR. To our knowledge, this is the first time that such categorization of rhinitis has been applied within an extensive literature review, usually all definitions of rhinitis being considered together within one term. We focused on a classification of rhinitis as an entity or according to its two main phenotypes: AR or NAR. Prevalences of other sub-phenotypes of rhinitis, such as rhino-conjunctivitis, are also of interest per se and should be assessed in more specific reviews.

F I G U R E 3 Evolution of allergic rhinitis prevalence worldwide over time
Overall, we found a median prevalence of 29% for unspecified rhinitis, which is close to the prevalence of 31.7% reported for children aged 13-14 years in the ISAAC phase 3 study. 8 However, a large variability was observed between the studies of rhinitis prevalence. This variability is probably partly explained by heterogeneity in the definitions used in the studies. Indeed, within the same population the prevalence was found to vary greatly depending on the definition used: for example, in the study by Bauchau et al. rhinitis prevalence in Belgium varied by more than 30% depending on whether rhinitis was defined based on doctor diagnosis or on reported symptoms. 39 Considering all the studies, we found that the average prevalence of doctor diagnosis-based definitions was lower compared to the other definitions. This could be partly explained by the fact that rhinitis prevalence is often underestimated when based on the doctor diagnosis. Indeed, it is recognized that patients with rhinitis often tend to self-diagnose their rhinitis and treat themselves, 40 and those who consult a doctor are likely to have more often moderate to severe rhinitis. 41 In addition, access to health professionals may be heterogeneous according to the geographic location, healthcare system, or socio-economic status of the patient.
Large variabilities in reported prevalences were also observed for AR SPT positivity to common aeroallergens. 44 These triggers as well as associated eye symptoms emerged as important discriminative variables in a clustering analysis that was performed without any a priori hypothesis to identify AR and NAR. 45  Rhinitis appears to be a common disease in the European and American countries, which is consistent with some previous reports. 4,5 In other parts of the world, far fewer studies have been reported on the prevalence of different types of rhinitis, which makes it more difficult to calculate reliable estimates and make firm conclusions. It is noteworthy that the global distribution of rhinitis prevalence was found to be similar to that of global distribution of asthma prevalence, for which there is more studies. 46 Further studies that apply standardized definitions of rhinitis in different parts of the world would throw more light on potential "true" differences in rhinitis prevalence and on potential causes underlying such differences.
Our extensive review showed that most studies reported an increase in rhinitis prevalence over time. One explanation could be that the awareness of rhinitis has improved in parallel in different populations around the world due to advertising of over-the-counter medicines for rhinitis, and with the development of the Internet mak- ing it easier to get information on rhinitis. In addition, medical examinations may have become better accessible and thus, the rhinitis diagnosis may also be more easily accessible. In any case, rhinitis prevalence seems to have increased in many parts of the world, whatever the definition of rhinitis. Concerning the trend of increasing prevalence of different types of rhinitis, potential impact of risk factors, including global warming, changes in seasonal patterns, and air pollution, have been proposed. 47 However, only few studies have investigated potential impact of such factors on rhinitis prevalence over time.
In conclusion, our review highlights the lack of consensus on which questions the phenotypes of rhinitis should be based. This review also found a geographical variability of rhinitis prevalences, and pointed out the scarcity or even inexistence of data from some parts of the world.
While these points could appear as not being novel, there is no recent literature review on this topic that would summarize these facts. The present extensive review underlines the urgent need for a consensus on standardized definitions for rhinitis to be used in epidemiological studies. Finally, for the first time in a literature review, this study shows that rhinitis prevalence in adults is increasing.

ACKNOWLEDGMENTS
This work is part of a thesis prepared in the framework of the Doctoral Network in Public Health coordinated by the EHESP. Marine